This proposal is submitted in response to RFA-ES-05-01, entitled "Superfund Basic Research Program". The contamination of groundwater and soils with As and Mn are associated with major public health, remedial, and environmental policy problems. Both Arsenic and manganese are found at numerous Superfund sites. This competitive renewal proposal seeks to obtain new knowledge, and train multidisciplinayr pre- and post-doctoral students, concerning the health effects, geochemistry, and remediation of As and Mn, with a particular focus on groundwater The proposed work involves substantial work at the single most seriously As-affected Superfund site in Vineland, NJ. It also involves epidemiologic studies of As- and Mn-exposed adults and children residing in Bangladesh and New Hampshire. As in the past, the Columbia University SBRP includes a unique balance between biomedical and non-biomedical research. The proposal includes four biomedical research projects: 1) Genotoxicity and Cell Signaling Pathways of As in Mammalian Cells; 2) Health Effects of Arsenic Cohort Study; 3) Consequences of As and Mn Exposure on Childhood Intelligence; and 4) One-Carbon Metabolism, Oxidative Stress, and Arsenic Toxicity. The biomedical research is intimately intertwined with three non-biomedical projects: 5) Mobilization of Natural Arsenic in Groundwater; 6) Mobilization of Anthropogenic Arsenic in Groundwater; and 7) Mitigation of Arsenic Mobilization in Groundwater. A Research Translation Core entitled, "Collaborating with government & the public: As & Mn exposure via groundwater" will work with several government agencies to help understand and solve their local groundwater problems. The Projects are supported by four Research Support Cores: 8) Data Management; 9) Trace Metals; 10) Biogeochemistry; and 11) Hydrogeology. Finally, a Training Core coordinates multi-disciplinary education and interaction among pre- and postdoctoral trainees who benefit from participation in the major inter-disciplinary research program..